Particulate air pollution is an important public health problem with respect to cardiovascular morbidity and mortality. Important strides have been made in understanding the neural and cardiac mechanisms involved. Heart rate variability analysis revealed important disturbances in autonomic tone during exposure to concentrated air particles (CAPs). We have obtained evidence in our canine models that CAPs may increase the severity of ischemia during acute coronary artery occlusion. These findings provide the direction for our studies, which are intended to expand our understanding of the mechanisms of air particulate exposure on the cardiovascular system. The specific aims are: 1) To determine the effect of ambient air particles on coronary hemodynamic function and arterial blood pressure in conscious dogs using CAPs exposures. 2) To determine whether the influence of ambient air particles on coronary artery blood flow and resistance is exacerbated by coronary artery stenosis in conscious dogs using CAPs exposures. Our studies will continue to employ the Harvard Ambient Particulate Concentrator (HAPC), a device that can increase ambient particle concentrations up to 30x without changing the physical or chemical characteristics of the particles; 2) a typical urban aerosol; 3) animal models of disease including myocardial ischemia in dogs to simulate the condition of compromised humans with ischemic heart disease, the primary substrate for adult cardiac mortality. The animals will be chronically instrumented with flow probes and telemetry devices to monitor arterial blood pressure and EKG. Coronary blood flow and pressure will be monitored in normal dogs and in dogs with partial coronary artery stenosis and compared during sympathetic or parasympathetic nerve blockade. The vasoactive balance controlled by endothelins and nitric oxide will be assessed during regulation of the coronary vascular response. The effects of components of pollutants will be systematically studied. Thus, the present application will entail unique application of comprehensive techniques to improve understanding of the mechanisms whereby CAPs can exert its deleterious influences on the heart and circulation [unreadable] [unreadable]